Association of the angiotensin I converting enzyme ( <i>ACE</i>) gene polymorphisms with recurrent aphthous stomatitis in the Czech population: case–control study

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Abstract

Background

Recurrent aphthous stomatitis (RAS) is multifactorial disease with unclear etiopathogenesis. The aim of this study was to determine distribution of the angiotensin I converting enzyme ( ACE) gene polymorphisms and their influence on RAS susceptibility in Czech population.

Methods

The study included 230 subjects (143 healthy controls and 87 patients with RAS) with anamnestic, clinical and laboratory data. Five ACE gene polymorphisms (rs4291/rs4305/rs4311/rs4331/rs1799752 = ACE I/D) were determined by TaqMan technique.

Results

The allele and genotype distributions of the studied ACE I/D polymorphisms were not significantly different between subjects with/without RAS ( P _corr > 0.05). However, carriers of II genotype were less frequent in the RAS group (OR = 0.48, 95% CI = 0.21–1.12, P = 0.059). Stratified analysis by sex demonstrated lower frequency of II genotype in women (OR = 0.33, 95% CI = 0.09–1.17, P < 0.035, P _corr > 0.05, respectively) than in men with RAS ( P > 0.05). Moreover, the frequency of AGTGD haplotype was significantly increased in RAS patients (OR = 13.74, 95% CI = 1.70–110.79, P = 0.0012, P _corr < 0.05). In subanalysis, TGD haplotype was significantly more frequent in RAS patients ( P < 0.00001) and CGI haplotype was less frequent in RAS patients ( P < 0.01), especially in women ( P = 0.016, P _corr > 0.05).

Conclusions

Our study indicates that while the AGTGD and TGD haplotypes are associated with increased risk of RAS development, CGI haplotype might be one of protective factors against RAS susceptibility in Czech population.

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Most cited references 38

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An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

P Corvol, B Rigat, F Soubrier … (1990)

A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.

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ACE polymorphisms.

Jacqueline Witteman, Anneke Oostra, M Lohuizen … (2006)

Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.

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Recurrent aphthous ulcers today: a review of the growing knowledge.

S S Natah, Y Konttinen, N S Enattah … (2004)

Recurrent aphthous ulcers represent a very common but poorly understood mucosal disorder. They occur in men and women of all ages, races and geographic regions. It is estimated that at least 1 in 5 individuals has at least once been afflicted with aphthous ulcers. The condition is classified as minor, major, and herpetiform on the basis of ulcer size and number. Attacks may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies. Local and systemic conditions, and genetic, immunological and microbial factors all may play a role in the pathogenesis of recurrent aphthous ulceration (RAU). However, to date, no principal cause has been discovered. Since the aetiology is unknown, diagnosis is entirely based on history and clinical criteria and no laboratory procedures exist to confirm the diagnosis. Although RAU may be a marker of an underlying systemic illness such as coeliac disease, or may present as one of the features of Behcet's disease, in most cases no additional body systems are affected, and patients remain otherwise fit and well. Different aetiologies and mechanisms might be operative in the aetiopathogenesis of aphthous ulceration, but pain, recurrence, self-limitation of the condition, and destruction of the epithelium seem to be the ultimate outcomes. There is no curative therapy to prevent the recurrence of ulcers, and all available treatment modalities can only reduce the frequency or severity of the lesions.

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Author and article information

Contributors

Lydie Izakovicova Holla: holla@med.muni.cz

Journal

Journal ID (nlm-ta): BMC Oral Health

Journal ID (iso-abbrev): BMC Oral Health

Title: BMC Oral Health

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6831

Publication date (Electronic): 19 March 2022

Publication date PMC-release: 19 March 2022

Publication date Collection: 2022

Volume: 22

Electronic Location Identifier: 80

Affiliations

[1 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Clinic of Stomatology, Institution Shared with St. Anne’s University Hospital, Faculty of Medicine, , Masaryk University, ; Pekarska 664/53, 60200 Brno, Czech Republic

[2 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Department of Pathophysiology, Faculty of Medicine, , Masaryk University, ; Kamenice 753/5, 62500 Brno, Czech Republic

[3 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Department of Biochemistry, Faculty of Science, , Masaryk University, ; Kamenice 753/5, 62500 Brno, Czech Republic

[4 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Czech National Centre for Evidence-Based Healthcare and Knowledge Translation (Cochrane Czech Republic, Czech EBHC: JBI Centre of Excellence, Masaryk University GRADE Centre), Institute of Biostatistics and Analyses, Faculty of Medicine, , Masaryk University, ; Kamenice 753/5, 62500 Brno, Czech Republic

[5 ]GRID grid.4491.8, ISNI 0000 0004 1937 116X, Department of Stomatology, General University Hospital in Prague and First Faculty of Medicine, , Charles University, ; Karlovo nam. 554/32, 12808 Prague, Czech Republic

[6 ]GRID grid.4491.8, ISNI 0000 0004 1937 116X, Institute of Immunology and Microbiology, General University Hospital in Prague and First Faculty of Medicine, , Charles University, ; Karlovo nam. 554/32, Prague, Czech Republic

[7 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Department of Clinical Immunology and Allergology, Institution Shared with St. Anne’s Faculty Hospital and Faculty of Medicine, , Masaryk University, ; Pekarska 664/53, 60200 Brno, Czech Republic

[8 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, RECETOX, Faculty of Science, , Masaryk University, ; Kotlarska 2, 61137 Brno, Czech Republic

[9 ]GRID grid.10267.32, ISNI 0000 0001 2194 0956, Institute of Biostatistics and Analyses, Faculty of Medicine, , Masaryk University, ; Kamenice 753/5, 62500 Brno, Czech Republic

Article

Publisher ID: 2115

DOI: 10.1186/s12903-022-02115-3

PMC ID: 8933959

PubMed ID: 35305614

SO-VID: c7cb6577-3842-46d3-88ae-fe00406902c8

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 24 November 2021

Date accepted : 9 March 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100010653, Masarykova Univerzita;

Award ID: MUNI/A/1445/2021

Award Recipient : Lydie Izakovicova Holla

Custom metadata

ScienceOpen disciplines: Dentistry

Keywords: recurrent aphthous stomatitis,angiotensin i converting enzyme,polymorphism,haplotype,sex difference

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ScienceOpen disciplines: Dentistry

Keywords: recurrent aphthous stomatitis, angiotensin i converting enzyme, polymorphism, haplotype, sex difference

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Association of the angiotensin I converting enzyme ( ACE) gene polymorphisms with recurrent aphthous stomatitis in the Czech population: case–control study

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Abstract

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International Journal of Medicine and Medical Research

Most cited references 38

An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

ACE polymorphisms.

Recurrent aphthous ulcers today: a review of the growing knowledge.

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Cited by 1

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